An increasing number of researchers use molecular dynamics (MD) simulations for research purposes such as identifying potential new drugs, identifying potential sites to mutate known proteins, and simulating protein-ligand interactions.
Two accepted methods have been reported for MD simulations of metalloproteins, such as the known zinc-bound proteins. The first is commonly referred to as the “bonded model.” The bonded model imposes a covalent bond between a metal cation, e.g., zinc, and its ligands to maintain the polyhedral geometry of the cation and its ligands during the MD simulations. There are disadvantages for the bonded model method including the inability to evaluate the intermolecular interactions of the metal cations with their ligands and the inability to simulate the exchanges of the ligands that coordinate to the metal ion. The second method is commonly referred to as the “non-bonded model.” The non-bonded model maintains a metal ion's geometry, e.g., zinc's polyhedral geometry, with electrostatic and van der Waals forces. The non-bonded model, however, is limited by the instability of such geometries during nanosecond MD simulations.
Accordingly, a dilemma facing researchers is the limitations of the conventional bonding models and methods for modeling bonding interactions of metal ions. Thus, there exists a need for improved methods for modeling metal-containing proteins.